Maternal/fetal interactions: the role of the MHC class I molecule HLA-G

The unique pattern of class I major histocompatibility complex (MHC) antigen expression seen at the human maternal/fetal interface is thought to be vital for fetal well-being. The lack of polymorphic class I and II MHC antigens on trophoblasts, the only fetal tissue in direct contact with the mother, is likely to be at least a part of the explanation of fetal evasion of allograft rejection. The recent observation that the HLA-G-encoded class I MHC molecule is present on certain subpopulations of cytotrophoblasts suggests that this nonpolymorphic molecule may have a role in the maternal/fetal immune response. Although no experimental evidence exists to support a particular function for HLA-G, reasoned speculation about the possible roles of this nonpolymorphic class I molecule is possible. Data derived from sequence analysis, analysis of HLA-G expression patterns, analysis of the extraembryonic expression patterns of other genes, and analysis of decidual lymphocyte phenotype and function provide insight into the possible functions of HLA-G at the maternal/fetal interface and are considered here.